Health-related quality of life (HRQOL) provides information on patients' everyday physical, emotional, and social difficulties that traditional measurements of asthma severity (pulmonary function assessments and asthma symptom scores) may not reflect. Our objective is to evaluate the effect of ciclesonide (CIC) on HRQOL in a combined analysis of two identical, 12-week, multicenter, double-blind, parallel-group, placebo-controlled trials. Patients (N=1015) with mild-to-moderate asthma (aged >or=12 years; forced expiratory volume in 1 s 60-85% predicted at randomization after administration of single-blind placebo during baseline [5-28 days]) were randomized to receive placebo or CIC 80, 160, or 320 microg (ex-actuator) once daily. HRQOL was assessed using the Juniper Asthma Quality-of-Life Questionnaire (AQLQ). The overall AQLQ score and individual domain scores (activity limitation, symptoms, emotional function, and exposure to environmental stimuli) were recorded at baseline, week 4 and week 12. Statistically significant improvements (p<0.0001) in overall AQLQ scores were observed for all CIC groups versus placebo (CIC80, 0.50; CIC160, 0.61; CIC320, 0.69; placebo, 0.14) from baseline to week 12. Similar significant improvements were observed for all CIC groups in the four individual domain scores, except the CIC80 environmental stimuli domain score. A greater proportion of CIC-treated patients achieved a minimally important difference in overall AQLQ score (>or=0.5 improvement) by week 4, which was sustained through to week 12, compared with placebo (week 12: CIC80, 47.1%; CIC160, 50%; CIC320, 50.6%; placebo, 31%). In this combined analysis, once-daily CIC significantly improved HRQOL compared with placebo, in adults/adolescents with mild-to-moderate persistent asthma.